To calculate pooled risk estimates for combinations of cytology result, human papillomavirus (HPV) 16/18 genotype and colposcopy impression to provide a basis for risk-stratified colposcopy and biopsy practice.
A PubMed search was conducted on June 1, 2016, and a ClinicalTrials.gov search was conducted on June 9, 2018, using key words such as “uterine cervical neoplasms,” “cervical cancer,” “mass screening,” “early detection of cancer,” and “colposcopy.”
Eligible studies must have included colposcopic impression and either cytology results or HPV 16/18 partial genotype results as well as a histologic biopsy diagnosis from adult women. Manuscripts were reviewed for the following: cytology, HPV status, and colposcopy impression as well as age, number of women, and number of cervical intraepithelial neoplasia (CIN) 2, CIN 3, and cancer cases. Strata were defined by the various combinations of cytology, genotype, and colposcopic impression.
Of 340 abstracts identified, nine were eligible for inclusion. Data were also obtained from three unpublished studies, two of which have since been published. We calculated the risk of CIN 2 or worse and CIN 3 or worse based on cytology, colposcopy, and HPV 16/18 test results. We found similar risk patterns across studies in the lowest risk groups such that risk estimates were similar despite different referral populations and study designs. Women with a normal colposcopy impression (no acetowhitening), less than high-grade squamous intraepithelial lesion cytology, and HPV 16/18-negative were at low risk of prevalent precancer. Women with at least two of the following: high-grade squamous intraepithelial lesion cytology, HPV16- or HPV18-positive, and high-grade colposcopic impression were at highest risk of prevalent precancer.
Our results support a risk-based approach to colposcopy and biopsy with modifications of practice at the lowest and highest risk levels.
Pooled estimates of risk of cervical intraepithelial neoplasia (CIN) 2 or worse and CIN 3 or worse in strata of colposcopy impression, cytology, and human papillomavirus genotyping support a risk-based approach to colposcopy and biopsy with modifications of practice at the lowest and highest risk levels.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland; BD Life Sciences, Franklin Lakes, New Jersey; Tulsa Cancer Institute, University of Oklahoma, School of Community Medicine, Tulsa, Oklahoma; the Department of Obstetrics and Gynecology, Department of Adult and Family Medicine, Kaiser Permanente Northern California, San Leandro, California; the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine in St. Louis, St. Louis, Missouri; the Department of Obstetrics and Gynecology, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts; and the Department of Obstetrics and Gynecology, University of Oklahoma, Oklahoma City, Oklahoma.
Corresponding author: Michelle I. Silver, PhD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Bethesda, MD 20850; email: firstname.lastname@example.org.
This work was funded by the Intramural Research Program of the National Cancer Institute (NCI). The NCI has received cervical cytology and human papillomavirus testing results for independent NCI-directed studies at reduced or no cost from Roche and Becton Dickinson.
Financial Disclosure Drs. Andrews, Cooper, and Parvu and are full-time employees of BD (Becton Dickinson & Company). Dr. Massad has received personal fees from malpractice firms for consultation on cases alleging missed cervical cancer, honoraria, and expenses for development of guidelines (2012 American Cancer Society cervical screening, 2013 American Society for Colposcopy and Cervical Pathology management) from the American Society for Colposcopy and Cervical Pathology. He served on a U.S. Food and Drug Administration advisory panel that recommended approval of primary human papillomavirus (HPV) screening by Roche assay. He has not had financial relationships with companies involved in manufacturing or marketing of HPV assays or HPV vaccine or diagnostic equipment or therapies. The other authors did not report any potential conflicts of interest.
Presented in part at the American Society for Colposcopy and Cervical Pathology Annual Meeting, April 19–21, 2018, Las Vegas, NV.
Each author has indicated that he or she has met the journal's requirements for authorship.
Received April 03, 2018
Received in revised form June 02, 2018
Accepted June 14, 2018